Trebananib With or Without Low-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia

NCT01555268 | Completed Phase 1

• 2 other identifiers: I 186010NCI-2011-02979
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the side effects and the best dose of trebananib when given together with or without low-dose cytarabine in treating patients with acute myeloid leukemia (AML). Trebananib may stop the growth of AML by blocking blood flow to the cancer. Drugs used in chemotherapy, such as cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving trebananib together with cytarabine may be an effective treatment for patients with AML.

Conditions

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (3)

• Safety of trebananib when administered alone and in combination with low-dose cytarabine measured by number of participants with toxicities according to CTCAE

  Adverse events will be tabulated overall and by arm.

  Up to 30 days after the last dose of study drug

• PK/PD profile of trebananib when administered alone

  A population PK/PD model will be developed to characterize the time course of AMG 386 concentrations in relation to target inhibition and hematological response. Model-predicted PK parameters will be generated, such as individual areas-under-the-curve (AUCs) and Cmax for AMG 386, to correlate with targeted biomarkers, such as Ang1, and Ang2, and VEGF as well as leukocyte count.

  Days 1, 3-5, 7, 8, 22, 24-26, and 29 of course 1

• PK/PD profile of trebananib when administered in combination with low-dose cytarabine

  A population PK/PD model will be developed to characterize the time course of AMG 386 concentrations in relation to target inhibition and hematological response. Model-predicted PK parameters will be generated, such as individual AUCs and Cmax for AMG 386, to correlate with targeted biomarkers, such as Ang1, and Ang2, and VEGF as well as leukocyte count.

  Days 1 and 7 of course 1

Secondary Outcomes (5)

• Clinical response in AML patients following trebananib therapy alone or given in combination with low-dose cytarabine therapy

  Up to 5 years

• Alterations in Ang1, Ang2, Tie2, VEGF, and VEGFR expression

  Up to 30 days post-treatment

• Changes in bone marrow vascularization and hypoxia

  Baseline up to 30 days post-treatment

• Changes in gene and/or microRNA expression

  Baseline up to 30 days post-treatment

• Characterization of time course of trebananib concentrations in relation to target inhibition and clinical response using PK/PD modeling

  Up to 5 years

Study Arms (2)

Arm A (trebananib)

EXPERIMENTAL

Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, and 22.

Biological: trebananib; Other: laboratory biomarker analysis; Other: pharmacological study

Arm B (trebananib, cytarabine)

EXPERIMENTAL

Patients receive trebananib as in Arm A. Patients also receive cytarabine SC BID on days 1-14 of course 1 and days 1-7 of subsequent courses.

Biological: trebananib; Drug: cytarabine; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

trebananib BIOLOGICAL

Given IV

Also known as: AMG 386, AMG386

Arm A (trebananib); Arm B (trebananib, cytarabine)

cytarabine DRUG

Given SC

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside

Arm B (trebananib, cytarabine)

laboratory biomarker analysis OTHER

Correlative studies

Arm A (trebananib); Arm B (trebananib, cytarabine)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm A (trebananib); Arm B (trebananib, cytarabine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of AML as defined by the World Health Organization (excluding acute promyelocytic leukemia and chronic myeloid leukemia- blast/accelerated phase) in an adult patient
• Patients with newly diagnosed untreated AML for whom the treatment of choice is low-intensity therapy by investigator assessment or who has declined intensive induction therapy recommended by the investigator OR
• Patients with refractory or relapsed AML following at least one prior treatment course who are not currently considered eligible for stem cell transplantation at the time of screening due to non-optimal AML disease control, lack of suitable transplantation donor, failure to meet other transplantation criteria, or refusal to undergo transplantation
• Eastern Cooperative Oncology Group (ECOG) status 0-2 (ECOG 3 is excluded)
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal (ULN)
• Creatinine clearance \> 40ml/min per 24 hour urine collection or calculated according to the Cockcroft-Gault formula
• Urinary protein quantitative value of less than 30mg/dL in urine analysis or less than 1+ on dipstick, unless quantitative protein is \< 1000mg in a 24 hour urine sample
• Partial thromboplastin time (PTT) or activated (aPTT) =\< 1.5 x ULN per institution laboratory range and international normalized ratio (INR) =\< 1.5
• Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
• Individuals of childbearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment

You may not qualify if:

• History of central nervous system involvement with leukemia
• History of venous or arterial thromboembolism within 12 months prior to enrollment
• History of clinically significant bleeding within 6 months of enrollment
• Unresolved toxicities from prior systemic therapies that are Common Terminology Criteria for Adverse Events (CTCAE) version 4 \>= Grade 2 in severity except alopecia excluding hematological toxicities attributable to underlying disease
• Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor
• Current or within 30 days prior to enrollment treatment with immune modulators such as systemic cyclosporine or tacrolimus
• Has not yet completed a 14 day washout period for any previous anti-cancer systemic therapies (30 days for prior bevacizumab) with the exception of hydroxyurea or leukapheresis for uncontrolled leukocytosis
• Enrolled in or has not yet completed at least 14 days since ending other investigational device or drug trials, or currently receiving other investigational treatments
• Clinically significant cardiovascular disease within 12 months prior to enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication or placement of percutaneous transluminal coronary angioplasty/stent
• Major surgery within 28 days prior to enrollment or still recovering from prior surgery
• Minor surgical procedures, placement of tunneled central venous access device within 3 days prior to enrollment
• Uncontrolled hypertension as defined as diastolic \> 90mmHg OR systolic \> 140mmHg; the use of anti-hypertensive medication to control hypertension is permitted
• Non-healing wound, ulcer (including gastrointestinal) or fracture
• Active uncontrolled infection, including human immunodeficiency virus (HIV) and active hepatitis infection
• Subject not consenting to the use of highly effective contraceptive, e.g., double barrier method (i.e., condom plus diaphragm) precautions during the course of the study and for 6 months after administration of the last study medication

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Amgen: collaborator

Study Sites (2)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

MeSH Terms

Conditions

Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute; Leukemia, Erythroblastic, Acute

Interventions

trebananib; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myeloproliferative Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Eunice Wang

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2012
• First Posted: March 15, 2012
• Study Start: October 31, 2011
• Primary Completion: September 24, 2013
• Study Completion: August 3, 2016
• Last Updated: September 13, 2022

Record last verified: 2022-09

Locations

US (2)